The HIPK2/CDC14B-MeCP2 axis enhances the spindle assembly checkpoint block by promoting cyclin B translation.

Mitotic perturbations activate the spindle assembly checkpoint (SAC) that keeps cells in prometaphase with high CDK1 activity. Prolonged mitotic arrest is eventually bypassed by gradual cyclin B decline followed by slippage of cells into G without chromosome segregation, a process that promotes cell transformation and drug resistance. Hitherto, the cyclin B1 decay is exclusively defined by mechanisms that involve its proteasomal degradation.

CDK1-cyclin-B1-induced kindlin degradation drives focal adhesion disassembly at mitotic entry.

The disassembly of integrin-containing focal adhesions (FAs) at mitotic entry is essential for cell rounding, mitotic retraction fibre formation, bipolar spindle positioning and chromosome segregation. The mechanism that drives FA disassembly at mitotic entry is unknown. Here, we show that the CDK1-cyclin B1 complex phosphorylates the integrin activator kindlin, which results in the recruitment of the cullin 9-FBXL10 ubiquitin ligase complex that mediates kindlin ubiquitination and degradation.

The human phosphatase CDC14A modulates primary cilium length by regulating centrosomal actin nucleation.

CDC14A codes for a conserved proline-directed phosphatase, and mutations in the gene are associated with autosomal-recessive severe to profound deafness, due to defective kinocilia. A role of CDC14A in cilia formation has also been described in other organisms. However, how human CDC14A impacts on cilia formation remains unclear.

The Kank family proteins in adhesion dynamics.

Integrin-mediated cell adhesion plays key roles for cell movement during development and tissue homeostasis. The dynamic life cycle of various integrin adhesions structures is required for the cell movements and regulated by the coordinated actions of both actomyosin and the microtubule (MT) cytoskeleton. The evolutionarily conserved Kank family proteins have emerged as regulators of adhesion dynamics by coordinating integrin-mediated force transmission with the recruitment of microtubules to integrins.

Human phosphatase CDC14A regulates actin organization through dephosphorylation of epithelial protein lost in neoplasm.

CDC14 is an essential dual-specificity phosphatase that counteracts CDK1 activity during anaphase to promote mitotic exit in Surprisingly, human CDC14A is not essential for cell cycle progression. Instead, it regulates cell migration and cell adhesion. Little is known about the substrates of hCDC14A and the counteracting kinases.

Human phosphatase CDC14A is recruited to the cell leading edge to regulate cell migration and adhesion.

Cell adhesion and migration are highly dynamic biological processes that play important roles in organ development and cancer metastasis. Their tight regulation by small GTPases and protein phosphorylation make interrogation of these key processes of great importance. We now show that the conserved dual-specificity phosphatase human cell-division cycle 14A (hCDC14A) associates with the actin cytoskeleton of human cells.

Genome editing through large insertion leads to the skipping of targeted exon.

Background: Highly efficient genome editing can be achieved through targeting an endonuclease to specific locus of interest. Engineered zinc-finger nuclease (ZFN) and CRISPR-associated protein-9 nuclease (Cas9) offer such an elegant approach for genome editing in vertebrate cells. In this study, we have utilized ZFN and Cas9-catalyzed double strand break followed by homologous recombination-mediated incorporation of premature stop codon and selection marker to target human cell division cycle 14A (hCDC14A) and cell division cycle 14B (hCDC14B) genes.

Global phosphoproteomic effects of natural tyrosine kinase inhibitor, genistein, on signaling pathways.

Genistein is a natural protein tyrosine kinase inhibitor that exerts anti-cancer effect by inducing G2/M arrest and apoptosis. However, the phosphotyrosine signaling pathways mediated by genistein are largely unknown. In this study, we combined tyrosine phosphoprotein enrichment with MS-based quantitative proteomics technology to globally identify genistein-regulated tyrosine phosphoproteins aiming to depict genistein-inhibited phosphotyrosine cascades.